Depression is a chronic illness involving the mind and body. It is also called “major depression,” “major depressive disorder,” and “clinical depression.” The American Psychiatric Association publishes a model for the classification of mental disorders. According to the model, “DSM-IV-TR,” a person is suffering from a major depressive episode if he or she experiences items 1 or 2 from the list of symptoms below, along with any four others, continuously for more than two weeks:                1. Depressed mood with overwhelming feelings of sadness and grief.        2. Apathy—loss of interest and pleasure in activities formerly enjoyed.        3. Sleep problems—insomnia, early-morning waking, or oversleeping nearly every day.        4. Decreased energy or fatigue.        5. Noticeable changes in appetite and weight (significant weight loss or gain).        6. Inability to concentrate or think, or indecisiveness.        7. Physical symptoms of restlessness or being physically slowed down.        8. Feelings of guilt, worthlessness, and helplessness.        9. Recurrent thoughts of death or suicide, or a suicide attempt.        
The prevalence of depression in the United States is profound, with almost 8% of the adult population suffering from at least one episode of major depression in the year 2007. The problem is serious and medications are insufficient to resolve the chronic illness for many adults.
Bipolar disorder affects about three percent of American men and women at some point in their lives. A person with the disorder typically has alternating periods of major depression and mania. In rare cases, mania can occur on its own. Episodes of mania are described as distinct periods of abnormally and persistently elevated, expansive, or irritable mood. Such episodes are severe enough to cause trouble at work, home, or both. The episodes can cause impaired judgment and often, excessive involvement in high-risk behavior. The time between episodes can vary greatly and men with bipolar disorder seem to have more manic episodes while women have more depressive episodes.
Generalized Anxiety Disorder (or “Anxiety” for short) is characterized by excessive, recurrent, and prolonged anxiety and worrying. See, Swartz, K. L., “The Johns Hopkins White Papers: Depression and Anxiety,” Johns Hopkins Medicine (2011) (hereafter, “Swartz 2011”). People with Anxiety typically agonize over everyday concerns like job responsibilities, finances, health, or family well-being. They may even agonize about minor matters like household chores, car repairs, being late for appointments, or personal appearances. The focus of such anxiety may shift from one concern to the next and the severity of sensations may range from mild tension and nervousness to feelings of dread.
Anxiety affects about three percent of adult Americans each year. While people with the disorder know that the intensity, duration and frequency of their anxiety are generally unreasonably high, long, or frequent, they still have difficulty controlling their emotions. Continued anxiety may impair concentration, memory, decision-making, attention span, and confidence. While the effect of Anxiety on everyday activities is generally known, Anxiety may also produce physical symptoms including heart palpitations, restlessness, sweating, headaches, and nausea.
The most common treatment options for depression, bipolar disorder and Anxiety are medications and psychotherapy. Disadvantageously, only about thirty percent of patients reach full remission after a first medication. Moreover, the side effects of medications are serious, including but not limited to weight gain, sexual dysfunction, nausea, drowsiness, and fatigue. It is important to start treatment for depression, bipolar disorder and Anxiety early because the illness becomes more difficult to treat after its initial onset. Further, patients respond to treatments differently. Hence, it becomes very important to try different medications and alternative treatments if the initial treatment(s) is not effective.
From the above, it is seen that alternatives for treating depression, bipolar disorder and Anxiety are needed. Some alternative treatments for depression, in addition to psychotherapy (which is a key component for treating any mood disorder), include electroconvulsive therapy, light therapy (mostly for seasonal affective disorder), and neuromodulation. Highly invasive neuromodulation approaches include deep brain stimulation (DBS) and vagus nerve stimulation. Other neuromodulation treatments include repetitive transcranial magnetic resonance stimulation (rTMS) and transcranial direct-current stimulation.
Deep brain stimulation, or DBS, is theoretically viewed as the best location for stimulation to treat disorders such as depression, bipolar disorder and Anxiety because it applies the stimulation at the very core, or root, of the problem. Disadvantageously, however, DBS is a very risky procedure, and unless the stimulation is applied precisely at the location within the brain where needed, and using precise stimulation currents, serious damage can be done to the brain. Thus, in practice, given the current state of the art, DBS is used sparingly.
An attractive alternative to providing electrical stimulation pulses deep inside the brain is to apply electrical stimulation pulses to various nerves which lead to the brain. The idea is that, using nerves as pathways or conduits to the inside of the brain, it is possible to send signals to key structures deep in the brain without penetrating into the skull.
One nerve that provides “a high-bandwidth pathway into the brain,” [quote attributed to Dr. Ian A. Cook, of the Semel Institute for Neuroscience and Human Behavior at UCLA, Los Angeles, Calif.], and which is the nerve (or its branches) used by some of the devices, methods and systems disclosed in this patent application to treat depression, bipolar disorder and Anxiety, is the Trigeminal nerve. The Trigeminal nerve is the fifth of 12 pairs of cranial nerves in the head. It is the nerve responsible for providing sensation to the face. One Trigeminal nerve runs to the right side of the head and the other to the left. Each of these nerves has three distinct branches. (“Trigeminal” derives from the Latin word “tria,” which means three, and “geminus,” which means twin.) After the Trigeminal nerve leaves the brain and travels inside the skull, it divides into three smaller branches, controlling sensations throughout the face.
The first branch of the Trigeminal nerve controls sensation in the eye, upper eyelid and forehead and is referred to as the “Opthalmic Nerve” or V1. The Supraorbital nerve is a part of this branch.
The second branch of the Trigeminal nerve controls sensation in the lower eyelid, cheek, nostril, upper lip and upper gum and is called the “Maxillary Nerve” or V2. Two prominent branches of the Maxillary nerve are the Zygomatic nerve and the Infraorbital nerve.
The third branch of the Trigeminal nerve controls sensations in the jaw, lower lip, lower gum and some of the muscles used for chewing. This third branch is called the “Mandibular Nerve” or V3.
The supraorbital nerve is a branch of the ophthalmic nerve (V). The supraorbital nerve courses from the forehead through the supraorbital notch (foramen) to join the supratrochlear nerve. The supratrochlear nerve carries information from the medial forehead, medial portion of the upper eyelid, and bridge of the nose.
U.S. Pat. No. 6,735,475, issued to Whitehurst et al., discloses use of an implantable miniature neurostimulator, referred to as a “microstimulator,” that can be implanted into a desired tissue location and used as a therapy for headache and/or facial pain. The microstimulator has a tubular shape, with electrodes at each end. Stimulation of the Trigeminal nerve is mentioned in the patent, but not for purposes of treating depression.
Other patents of Whitehurst et al. teach the use of this small, microstimulator, placed in other body tissue locations, including within an opening extending through the skull into the brain, for the treatment of a wide variety of conditions, disorders and diseases. See, e.g., U.S. Pat. No. 6,950,707 (obesity and eating disorders); U.S. Pat. No. 7,003,352 (epilepsy by brain stimulation); U.S. Pat. No. 7,013,177 (pain by brain stimulation); U.S. Pat. No. 7,155,279 (movement disorders through stimulation of Vagus nerve with both electrical stimulation and drugs); U.S. Pat. No. 7,292,890 (Vagus nerve stimulation); U.S. Pat. No. 7,203,548 (cavernous nerve stimulation); U.S. Pat. No. 7,440,806 (diabetes by brain stimulation); U.S. Pat. No. 7,610,100 (osteoarthritis); and U.S. Pat. No. 7,657,316 (headache by stimulating motor cortex of brain).
Recently, some promising experimental neuromodulation approaches for the treatment of depression through stimulation of the Trigeminal nerve have appeared. See, e.g., “Non-Invasive Therapy Significantly Improves Depression, Researchers Say,” ScienceDaily.com (Sep. 6, 2010); “Trigeminal nerve stimulation significantly improves depression”, www.psypost.org, Friday, Sep. 3, 2010; Lewis, D. “Trigeminal Nerve Stimulation for Depression,” www.helpforDpression.com (Sep. 15, 2011).
Further, there is at least one company, NeuroSigma, Inc., of Westwood, Calif., that is developing and commercializing neuromodulation treatments for a variety of disorders, including epilepsy, depression, post-traumatic stress disorder (PTSD), obesity, and cachexia. The therapy platforms used by NeuroSigma at the present comprise Trigeminal Nerve Stimulation (TNS) and Deep Brain Stimulation (DBS). See, e.g., the web site of NeuroSigma, Inc., found at http://www.neurosigma.com/.
U.S. Patent Publications of DeGiorgio et al., US 2011/0106220, published May 5, 2011; US 2011/0112603 A1, published May 12, 2011; US 2011/0218859 A1, published Sep. 8, 2011; and US 2011/0218590 A1, published Sep. 8, 2011, describe and disclose, in some detail, the devices and methods used by NeuroSigma, Inc. in carrying out its TNS therapy platform for the treatment of depression and epilepsy, and other neurological or neuropsychiatric disorders. The four published patent applications referenced in this paragraph are incorporated herein by reference in their entireties. These four published patent applications appear to be assigned to The Regents of the University of California. The Regents of the University of California, in turn, appear to have recently executed an exclusive worldwide license for Trigeminal Nerve Stimulation (TNS) with NeuroSigma Inc., as reported in Science Daily (Sep. 6, 2010). See, e.g., the news release found at http://www.sciencedaily.com/releases/2010/09/110903092507.htm.
In general, two of the above four published US patent applications of DeGiorgio et al., US 2011/0112603 A1, published May 12, 2011 (hereafter the “603 Publication”) and US 2011/0218590 A1, published Sep. 8, 2011 (hereafter the “'590 Publication”), relate primarily to TNS stimulation for treatment of depression and other mood disorders using either cutaneous electrodes ('590 Publication) or using at least one implantable electrode ('603 Publication). The other two of the above four published US Patent applications, US 2011/0106220, published May 5, 2011 (hereafter the “'220 Publication”) and US 2011/0218859 A1, published Sep. 8, 2011 (hereafter the “859 Publication”), relate primarily to TNS stimulation for treatment of epilepsy and other neurological disorders and conditions using either cutaneous electrodes ('589 Publication) or using at least one implantable electrode ('220 Publication).
In the two DeGiorgio et al. published patent applications where an implantable electrode is used, electrical connection with the implantable electrode occurs by either (i) connecting an implanted electrical cable between the implantable electrode contacts and an implanted neurostimulator, see, e.g., the '603 Publication at Paragraph [0060], or (ii) making a wireless electrical connection between an external, non-implanted neurostimulator and the implantable electrode assembly through the use of inductive coupling. Id. Either way, when implantable electrode contacts are employed, there must either be significant tunneling through the tissue to allow a connecting cable to make electrical connection between the implanted neurostimulator device and electrode contacts, or additional circuitry with its accompanying complexity (and associated increased power consumption) must be employed within the external neurostimulator and/or the implanted electrode contacts to facilitate an enhanced inductively coupled connection.
Insofar as Applicant is aware, the '603 Publication represents the current state of the art for treating depression using implantable devices and methods that stimulate the Trigeminal nerve. Similarly, the '220 Publication represents the current state of the art for treating epilepsy using implantable devices and methods that stimulate the Trigeminal nerve. However, while the advance in the art described and presented in the '603 and '220 Publications is significant over prior neuromodulation therapy techniques for treating depression or epilepsy, improvements are still needed. For example, when implantable electrode contacts are employed, an efficient and safe mechanism must still be employed to electrically (or optically, or magnetically) connect the electrode contacts to a suitable pulse generator. If the pulse generator is external (non-implanted), either (i) the leads must pass through the skin (not a good thing to do over time because of infections and other concerns), or (ii) some sort of signal coupling mechanism, such as inductive or rf coupling, must be employed to allow the pulses generated by the pulse generator to be efficiently transferred to the electrode array and to specific electrode contacts included within the electrode array. If the pulse generator is implanted, a cable or lead must be tunneled through the body tissue from the implant location of the pulse generator to the implant location of the electrode contacts. Tunneling through body tissue, especially over a long distance, suffers from all the same risks associated with major surgery, as well as creates problems for the patient in the event of lead malfunction or breakage. Thus, it is seen that despite the advances made in the art, improvements are still needed.
Another alternative approach for treating depression, bipolar disorder and Anxiety, and a host of other physiological conditions, illnesses and deficiencies, is acupuncture, which includes traditional acupuncture, acupressure. Acupuncture has been practiced in Eastern civilizations (principally China, but also other Asian countries) for at least 2500 years. It is still practiced today throughout many parts of the world, including the United States and Europe. A good summary of the history of acupuncture, and its potential applications, may be found in Cheung, et al., “The Mechanism of Acupuncture Therapy and Clinical Case Studies”, (Taylor & Francis, publisher) (2001) ISBN 0-415-27254-8, hereafter referred to as “Cheung, Mechanism of Acupuncture, 2001.” The Forward, as well as Chapters 1-3, 5, 7, 8, 12 and 13 of Cheung, Mechanism of Acupuncture, 2001, are incorporated herein by reference.
Despite the practice in Eastern countries for over 2500 years, it was not until President Richard Nixon visited China (in 1972) that acupuncture began to be accepted in Western countries, such as the United States and Europe. One of the reporters who accompanied Nixon during his visit to China, James Reston, from the New York Times, received acupuncture in China for post-operative pain after undergoing an emergency appendectomy under standard anesthesia. Reston experienced pain relief from the acupuncture and wrote about it in The New York Times. In 1973 the American Internal Revenue Service allowed acupuncture to be deducted as a medical expense. Following Nixon's visit to China, and as immigrants began flowing from China to Western countries, the demand for acupuncture increased steadily. Today, acupuncture therapy is viewed by many as a viable alternative form of medical treatment, alongside Western therapies. Moreover, acupuncture treatment is now covered, at least in part, by most insurance carriers. Further, payment for acupuncture services consumes a not insignificant portion of healthcare expenditures in the U.S. and Europe. See, generally, Cheung, Mechanism of Acupuncture, 2001, vii.
Acupuncture is an alternative medicine that treats patients by insertion and manipulation of needles in the body at selected points. Novak, Patricia D. et al (1995). Dorland's Pocket Medical Dictionary (25th ed.). Philadelphia: (W.B. Saunders Publisher). ISBN 0-7216-5738-9. The locations where the acupuncture needles are inserted are referred to herein as “acupuncture points” or simply just “acupoints”. The location of acupoints in the human body has been developed over thousands of years of acupuncture practice, and maps showing the location of acupoints in the human body are readily available in acupuncture books or online. For example, see, “Acupuncture Points Map,” found online at: http://www.acupuncturehealing.org/acupuncture-points-map.html, Acupoints are typically identified by various letter/number combinations, e.g., L6, S37. The maps that show the location of the acupoints may also identify what condition, illness or deficiency the particular acupoint affects when manipulation of needles inserted at the acupoint is undertaken.
References to the acupoints in the literature are not always consistent with respect to the format of the letter/number combination. Some acupoints are identified by a name only, e.g., Tongli. The same acupoint may be identified by others by the name followed with a letter/number combination placed in parenthesis, e.g., Tongli (HT5). Alternatively, the acupoint may be identified by its letter/number combination followed by its name, e.g., HT5 (Tongli). The first letter typically refers to a body organ, or other tissue location associated with, or affected by, that acupoint. However, usually only the letter is used in referring to the acupoint, but not always. Thus, for example, the acupoint GV20 is the same as acupoint Governing Vessel 20 which is the same as GV-20 which is the same as GV 20 which is the same as Baihui. For purposes of this patent application, unless specifically stated otherwise, all references to acupoints that use the same name, or the same first letter and the same number, and regardless of slight differences in second letters and formatting, are intended to refer to the same acupoint.
An excellent reference book that identifies all of the traditional acupoints within the human body is WHO STANDARD ACUPUNCTURE POINT LOCATIONS IN THE WESTERN PACIFIC REGION, published by the World Health Organization (WHO), Western Pacific Region, 2008 (updated and reprinted 2009), ISBN 978 92 9061 248 7 (hereafter “WHO Standard Acupuncture Point Locations 2008”). The Table of Contents, Forward (page v-vi) and General Guidelines for Acupuncture Point Locations (pages 1-21), as well as pages 203 and 213 (which pages illustrate with particularity the location of acupoint GV20) of the WHO Standard Acupuncture Point Locations 2008, and page 185 of The Teaching Atlas of Acupuncture, see, Quirico P E, Pedrali T. Teaching Atlas of Acupuncture, Volume 1: Channels and Points. Georg Thieme Verlag. 2007, (which illustrates the location of acupoint EX Yintang, also referred to as acupoint EXHN3), are included herewith as Appendix D.
While many in the scientific and medical community are highly critical of the historical roots upon which acupuncture has developed, (e.g., claiming that the existence of meridians, qi, yin and yang, and the like have no scientific basis), see, e.g., http://en.wikipedia.org/wiki/Acupuncture, few can refute the vast amount of successful clinical and other data, accumulated over centuries of acupuncture practice, that shows needle manipulation applied at certain acupoints is quite effective.
The World Health Organization and the United States' National Institutes of Health (NIH) have stated that acupuncture can be effective in the treatment of neurological conditions and pain. Reports from the USA's National Center for Complementary and Alternative Medicine (NCCAM), the American Medical Association (AMA) and various USA government reports have studied and commented on the efficacy of acupuncture. There is general agreement that acupuncture is safe when administered by well-trained practitioners using sterile needles, but not on its efficacy as a medical procedure.
An early critic of acupuncture, Felix Mann, who was the author of the first comprehensive English language acupuncture textbook Acupuncture: The Ancient Chinese Art of Healing, stated that “The traditional acupuncture points are no more real than the black spots a drunkard sees in front of his eyes.” Mann compared the meridians to the meridians of longitude used in geography—an imaginary human construct. Mann, Felix (2000). Reinventing acupuncture: a new concept of ancient medicine. Oxford: Butterworth-Heinemann. pp. 14; 31. ISBN 0-7506-4857-0. Mann attempted to combine his medical knowledge with that of Chinese theory. In spite of his protestations about the theory, however, he apparently believed there must be something to it, because he was fascinated by it and trained many people in the West with the parts of it he borrowed. He also wrote many books on this subject. His legacy is that there is now a college in London and a system of needling that is known as “Medical Acupuncture”. Today this college trains doctors and Western medical professionals only.
For purposes of this patent application, the arguments for and against acupuncture are interesting, but not that relevant. What is important is that a body of literature exists that identifies several acupoints within the human body that, rightly or wrongly, have been identified as having an influence on, or are otherwise somehow related to, the treatment of various physiological conditions, deficiencies or illnesses, including pain and other conditions associated with myocardial ischemia, such as angina pectoris. With respect to these acupoints, the facts speak for themselves. Either these points do or do not affect the conditions, deficiencies or illnesses with which they have been linked. The problem lies in trying to ascertain what is fact from what is fiction. This problem is made more difficult when conducting research on this topic because the insertion of needles, and the manipulation of the needles once inserted, is more of an art than a science, and results from such research become highly subjective. What is needed is a much more regimented approach for doing acupuncture research.
It should also be noted that other medical research, not associated with acupuncture research, has over the years identified nerves and other locations throughout a patient's body where the application of electrical stimulation produces a beneficial effect for the patient. Indeed, the entire field of neurostimulation deals with identifying locations in the body where electrical stimulation can be applied in order to provide a therapeutic effect for a patient. For purposes of this patent application, such known locations within the body are treated essentially the same as acupoints—they provide a “target” location where electrical stimulation may be applied to achieve a beneficial result, whether that beneficial result is to reduce pain, to treat myocardial ischemia, to treat hypertension, to treat cardiovascular disease, to treat depression, or to mitigate some other form of mental disorder (e.g., Anxiety, bipolar disorder) or condition of the patient.
Returning to the discussion regarding acupuncture, some have proposed applying moderate electrical stimulation at selected acupuncture points through needles that have been inserted at those points. See, e.g., http://en.wikipedia.org/wiki/Electroacupuncture. Such electrical stimulation is known as electroacupuncture (EA). According to Acupuncture Today, a trade journal for acupuncturists: “Electroacupuncture is quite similar to traditional acupuncture in that the same points are stimulated during treatment. As with traditional acupuncture, needles are inserted on specific points along the body. The needles are then attached to a device that generates continuous electric pulses using small clips. These devices are used to adjust the frequency and intensity of the impulse being delivered, depending on the condition being treated. Electroacupuncture uses two needles at a time so that the impulses can pass from one needle to the other. Several pairs of needles can be stimulated simultaneously, usually for no more than 60 minutes at a time.” “Acupuncture Today: Electroacupuncture”. 2004 Feb. 1 (retrieved on-line Aug. 9, 2006 at http://www.acupuncturetoday.com/abc/electroacupuncture.php).
Similar techniques for using electrical devices, including external EA devices, for stimulating peripheral nerves and other body locations for treatment of various maladies are known in the art. See, e.g., U.S. Pat. Nos. 4,535,784; 4,566,064; 5,195,517; 5,250,068; 5,251,637; 5,891,181; 6,393,324; 6,006,134; 7,171,266; and 7,171,266. The methods and devices disclosed in these patents, however, typically utilize either large implantable stimulators having long leads that must be tunneled through tissue to reach the desired stimulation site, or use external devices that must interface with implanted electrodes via percutaneous leads or wires passing through the skin. Such devices and methods are still far too invasive, or are ineffective, and thus are subject to the same limitations and concerns, as are the previously described electrical stimulation devices.
From the above, it is seen that there is a need in the art for a less invasive device and technique for electroacupuncture stimulation of acupoints that does not require the continual use of needles inserted through the skin, or long insulated wires implanted or inserted into blood vessels, for the purposes of treating mental disorders, such as depression, Anxiety, or bi-polar disorder.